Recent data demonstrates that the peripheral immune system has important effects on neuronal integrity and function in the CNS. This data includes work from our lab and others showing that deficits in neurobehavioral performance and motor neuron regeneration following axotomy are associated with the absence of functional T and B lymphocytes in immunodeficient mice. Moreover, alterations in neuronal function in immunodeficient mice can be prevented if normal lymphocytes from wild-type mice of the same genetic background are adoptively transferred to reconstitute a functional immune system in these animals. The proposed studies are designed to elucidate the neurobiological and immunological mechanisms that modulate these important processes in both limbic and motor neurons. The Specific Aims will identify critical mechanisms that determine whether immunological processes are involved in modulating parameters of brain function and behavior, and may have proregenerative effects on injured neurons. These aims are: 1) Test the hypothesis that immune status during development serves as a determinant of behavior; 2) Test the hypothesis that immunodeficiency results in alterations in septal and hippocampal neurons; and 3) Test the hypotheses that the proregenerative effects of immune reconstitution are mediated principally by T lymphocytes, and that their proregenerative function may be augmented by prior exposure to neuronal damage.